Cells and tissues in vivo are subjected to various forms of mechanical forces that are essential to their normal development and functions. The arterial blood vessel wall is continuously exposed to mechanical stresses such as pressure, strain, and shear due to the pulsatile nature of blood flow. Vascular smooth muscle cells (SMCs) populate the media of blood vessels and play important roles in the control of vasoactivity and the remodeling of the vessel wall. It is well documented that the phenotype and functions of vascular SMCs are not only regulated by chemical factors such as transforming growth factor-beta(1) (TGF-beta(1)), but also by mechanical factors such as uniaxial strain. The purpose of our study was to explore the effects of TGF-beta(1) alone or in combination with uniaxial cyclic strain on adipose-derived stem cell (ASC) morphology, proliferation, and differentiation. Low passage ASCs were stimulated with 10% strain at 1 Hz for 7 days, with or without TGF-beta(1). Cyclic strain inhibited proliferation, and caused alignment of the cells and of the F-actin cytoskeleton perpendicular to the direction of strain. Strain alone resulted in a decrease in the expression of early SMC markers alpha-SMA and h (1)-calponin. While the response of SMCs and other progenitor cells such as bone marrow stromal cells to mechanical forces has been extensively studied, the roles of these forces on ASCs remain unexplored. This work advances our understanding of the mechanical regulation of ASCs.